Having gained some insight into the pathogenesis of periodontal disease by a comparative ultrastructural study of germ free and monoinfected rat periodontal tissues we propose to extend our understanding of the mechanisms of tissue destruction by a combined light and electron microscopic investigation of the effects of experimentally induced inflammation on the ultrastructure of the periodontium in conventional rats. That within the inflammatory process itself, irrespective of the nature of the irritating agent, may lie the causative factors responsible for resorption of alveolar bone and breakdown of the periodontal ligament is the premise upon which this proposal is based. We propose to induce inflammation by the injection of substances known to be capable of promoting inflammation. Those substances are antigen-antibody complexes, endotoxin and kallikrein. The changes produced on the periodontium (with special emphasis on vascular components, fibroblasts, and alveolar bone cells) will be assessed by electron microscopic and histochemical techniques. Previous knowledge obtained in an electron microscopic study of germ free rat periodontal tissues will provide an important source of control data (see progress report). Part of this research plan will include an investigation of the penetration of sulcular epithelium by peroxidase and cytochrome C. The size of the intercellular spaces will be studied by use of freeze- fracture techniques. This will provide us with a better understanding of the epithelium as a barrier to antigenic and inflammatory substances. The effects of intraperitoneal inflammation on the diffusion chamber culture of bone within the peritoneal cavity will be investigated.